Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Mechanism of Inhibition of Joint Destruction by Rituximab in Rheumatoid Arthritis.
Boumans2, Maria J. H., Thurlings3, Rogier M., Vos4, Koen, Gerlag3, Danielle M., Tak1, Paul P.
Academic Med Ctr/Univ of Amsterdam, Amsterdam, The Netherlands
Academic Medical Center/University of Amsterdam, Amsterdam, Noord-Holland, The Netherlands
Academic Medical Center/University of Amsterdam
Academic Medical Center/University of Amsterdam/Jan van Breemen Institute
The RANK/RANKL/OPG system regulates osteoclast differentiation and activation. Osteoclasts are essential for the resorption of mineralised cartilage and subchondral bone in chronic arthritis. Treatment with rituximab may reduce the progression of joint destruction in rheumatoid arthritis (RA) patients, even in the absence of a clinical response. The underlying mechanisms are at present poorly understood.
To examine the effects of rituximab treatment on the RANK/RANKL/OPG system.
Twenty-eight rheumatoid factor positive and/or ACPA positive RA patients were treated with rituximab. Methylprednisolone pre-medication was omitted to study the specific effects of rituximab. Serum OPG was measured using multiplex analysis before and 16 weeks after treatment. Serum RANKL was measured by ELISA. OPG and RANK expression was measured in synovial biopsy samples of 20 patients before and 16 weeks after treatment using immunohistochemistry. Stained sections were evaluated by digital image analysis. Changes after treatment were assessed using the Wilcoxon's signed rank test.
We found a significant decrease in serum levels of both OPG and RANKL 16 weeks after initiation of rituximab treatment (20 %, P= 0.001 and 40 %, P= < 0.0001 respectively) while the OPG/RANKL ratio increased (P= 0.006). In the synovial tissue, there was a significant decrease of 99 % in RANK-positive osteoclast precursors (P= 0.018), while OPG expression showed a non-significant decrease (25 %, P= 0.069).
The decrease in synovial osteoclast precursors associated with the increased OPG/RANKL ratio in the serum may explain in part the protective effect of rituximab treatment against progression of joint destruction.
To cite this abstract, please use the following information:
Boumans, Maria J. H., Thurlings, Rogier M., Vos, Koen, Gerlag, Danielle M., Tak, Paul P.; Mechanism of Inhibition of Joint Destruction by Rituximab in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1821